Antibody Inhibition of a Viral Type 1 Interferon Decoy Receptor Cures a Viral Disease by Restoring Interferon Signaling in the Liver

Details

• Alternative Title:
  PLoS Pathog
• Personal Author:
  Xu, Ren-Huan ; Rubio, Daniel ; Roscoe, Felicia ; Krouse, Tracy E. ; Truckenmiller, Mary Ellen ; Norbury, Christopher C. ; Hudson, Paul N. ; Damon, Inger K. ; Alcamí, Antonio ; Sigal, Luis J.
• Description:
  Type 1 interferons (T1-IFNs) play a major role in antiviral defense, but when or how they protect during infections that spread through the lympho-hematogenous route is not known. Orthopoxviruses, including those that produce smallpox and mousepox, spread lympho-hematogenously. They also encode a decoy receptor for T1-IFN, the T1-IFN binding protein (T1-IFNbp), which is essential for virulence. We demonstrate that during mousepox, T1-IFNs protect the liver locally rather than systemically, and that the T1-IFNbp attaches to uninfected cells surrounding infected foci in the liver and the spleen to impair their ability to receive T1-IFN signaling, thus facilitating virus spread. Remarkably, this process can be reversed and mousepox cured late in infection by treating with antibodies that block the biological function of the T1-IFNbp. Thus, our findings provide insights on how T1-IFNs function and are evaded during a viral infection in vivo, and unveil a novel mechanism for antibody-mediated antiviral therapy.
• Subjects:
  Animals Antibodies, Viral Cell Line Cricetinae Ectromelia, Infectious Ectromelia Virus Female Liver Mice Mice, Inbred BALB C Mice, SCID Receptor, Interferon Alpha-beta Spleen Variola Virus Viral Proteins Virulence Factors Virus Attachment

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• Source:
  PLoS Pathog. 2012; 8(1).
• Document Type:
  Journal Article
• Volume:
  8
• Issue:
  1
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:652a2952f1521822e2669fbf9df0d6bc11c89be28451005c933e71f45cfffe5e
• Download URL:
  https://stacks.cdc.gov/view/cdc/8203/cdc_8203_DS1.pdf
• File Type:
  [PDF - 1.84 MB ]